title: Delays in appropriate antibiotic therapy for gram-negative bloodstream infections: a multicenter, community hospital study.
abstract: BACKGROUND
  Gram-negative bacterial bloodstream infection (BSI) is a serious condition with estimated 30% mortality. Clinical outcomes for patients with severe infections improve when antibiotics are appropriately chosen and given early. The objective of this study was to estimate the association of prior healthcare exposure on time to appropriate antibiotic therapy in patients with gram-negative BSI.
  
  
  METHODS
  We performed a multicenter cohort study of adult, hospitalized patients with gram-negative BSI using time to event analysis in nine community hospitals from 2003-2006. Event time was defined as the first administration of an antibiotic with in vitro activity against the infecting organism. Healthcare exposure status was categorized as community-acquired, healthcare-associated, or hospital-acquired. Time to appropriate therapy among groups of patients with differing healthcare exposure status was assessed using Kaplan-Meier analyses and multivariate Cox proportional hazards models.
  
  
  RESULTS
  The cohort included 578 patients with gram-negative BSI, including 320 (55%) healthcare-associated, 217 (38%) community-acquired, and 41 (7%) hospital-acquired infections. 529 (92%) patients received an appropriate antibiotic during their hospitalization. Time to appropriate therapy was significantly different among the groups of healthcare exposure status (log-rank p=0.02). Time to first antibiotic administration regardless of drug appropriateness was not different between groups (p=0.3). The unadjusted hazard ratios (HR) (95% confidence interval) were 0.80 (0.65-0.98) for healthcare-associated and 0.72 (0.63-0.82) for hospital-acquired, relative to patients with community-acquired BSI. In multivariable analysis, interaction was found between the main effect and baseline Charlson comorbidity index. When Charlson index was 3, adjusted HRs were 0.66 (0.48-0.92) for healthcare-associated and 0.57 (0.44-0.75) for hospital-acquired, relative to patients with community-acquired infections.
  
  
  CONCLUSIONS
  Patients with healthcare-associated or hospital-acquired BSI experienced delays in receipt of appropriate antibiotics for gram-negative BSI compared to patients with community-acquired BSI. This difference was not due to delayed initiation of antibiotic therapy, but due to the inappropriate choice of antibiotic.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, United States of America ; Department of Medicine, Division of Infectious Diseases, Durham Veterans Affairs Medical Center, Durham, North Carolina, United States of America.
authors.forename: Rebekah W
authors.initials: RW
authors.lastname: Moehring
authors.forename: Richard
authors.initials: R
authors.lastname: Sloane
authors.forename: Luke F
authors.initials: LF
authors.lastname: Chen
authors.forename: Emily C
authors.initials: EC
authors.lastname: Smathers
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Schmader
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sexton
authors.forename: Deverick J
authors.initials: DJ
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000188:drug therapy; D003428:Cross Infection / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D006764:Hospitals, Community; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents